Biomedical and Biotechnology Research Journal (BBRJ)

LETTER TO EDITOR
Year
: 2020  |  Volume : 4  |  Issue : 5  |  Page : 106--107

Potential therapeutic effects of pentoxifylline against COVID-19


Atefeh Abedini1, Faezeh Feizabadi2, Arda Kiani3, Farzaneh Dastan4,  
1 Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Tracheal Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
4 Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD); Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Correspondence Address:
Dr. Farzaneh Dastan
Chronic Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran, Department of Clinical Pharmacy, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran
Iran




How to cite this article:
Abedini A, Feizabadi F, Kiani A, Dastan F. Potential therapeutic effects of pentoxifylline against COVID-19.Biomed Biotechnol Res J 2020;4:106-107


How to cite this URL:
Abedini A, Feizabadi F, Kiani A, Dastan F. Potential therapeutic effects of pentoxifylline against COVID-19. Biomed Biotechnol Res J [serial online] 2020 [cited 2022 Jul 7 ];4:106-107
Available from: https://www.bmbtrj.org/text.asp?2020/4/5/106/292075


Full Text



Sir,

At present, the novel coronavirus disease (COVID-19), a contagious and pandemic disease that leads to mortality, is a significant global concern. The exact cause of the enormous inflammation induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Nonetheless, the p38 mitogen-activated protein kinase (MAPK) system is one of the precise pathways that have been previously implicated in animal models of acute lung injury and myocardial injury.[1] For replication purposes, the SARS-CoV-2, like other RNA respiratory viruses, may precisely upregulate p38 MAPK. It has been shown that activation of proinflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-1β, can be caused by the upregulation of the p38 MAPK pathway. In addition, overactivation of the p38 MAPK system, facilitation of cell entry through endocytosis by viral receptors, propagation of the SARS-CoV-2 viral lifecycle, aggregation of platelets, arterial thrombosis, apoptosis of endothelial cells, impairment of contractility in cardiomyocytes, hypoxic pulmonary vasoconstriction, and vascular remodeling can all occur and cause severe impairments in patients with COVID-19 infection. Therefore, therapeutic inhibition of the p38 MAPK system should be considered for patients at risk for severe COVID-19 complications.[2]

In one study, pentoxifylline, as a modulatory agent, was demonstrated to have effects on the p38 MAPK system of a rat model. The authors showed that pentoxifylline could suppress cyclooxygenase-2 expression, increase matrix metallopeptidase 9 expression, and downregulate p38 pathway activation in cerebral ischemia-reperfusion injury rats in vivo.[3] In addition, other studies have demonstrated that pentoxifylline can downregulate proinflammatory cytokines and proliferating cells in lung tissue and has favorable effects in inflammatory conditions, such as HTLV-I-associated myelopathy, asthmatic bronchial inflammation, and acute respiratory distress syndrome (ARDS).[4] Thein vivo capability of pentoxifylline to inhibit TNF secretion in patients with ARDS may decrease patient complications.[5] Moreover, Amvros'eva et al. reported pentoxifylline-mediated inhibition of thein vitro replication of several viruses, such as herpes simplex virus, vaccinia virus, rotavirus, and tick-borne encephalitis virus.[6]

Pentoxifylline exhibits complex functions with extensive pharmacological impacts and is used therapeutically because of its efficacy and rapid metabolism in the body, with no cumulative effects and few side effects.[3]

The potential value of pentoxifylline as an antiproliferative and antifibrogenic agent has been indicated based on growing evidence. Both basal and transforming growth factor-β1-augmented collagen α1 and collagen α1 mRNA levels beginning at 24 h and later at 48 h were suppressed by pentoxifylline. According to these data, the antimutagenic and anti-collagenase effects of pentoxifylline were mediated predominantly through the cyclic adenosine monophosphate/protein kinase A effector pathway.[7]

Pentoxifylline has anti-inflammatory, antiviral, antifibrotic, antithrombotic, immunomodulatory, and bronchodilatory properties. Its low cost and minimal toxicity are among the beneficial effects that favor this agent to be considered for COVID-19 patients to reduce various complications, such as lung and myocardial injuries. Based on the variety of benefits of pentoxifylline, it can be considered a potential treatment option for COVID-19.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

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2Grimes JM, Grimes KV. p38 MAPK inhibition: A promising therapeutic approach for COVID-19. J Mol Cell Cardiol 2020;144:63-5.
3Dong J, Yuan X, Xie W. Pentoxifylline exerts anti-inflammatory effects on cerebral ischemia reperfusion-induced injury in a rat model via the p38 mitogen-activated protein kinase signaling pathway. Mol Med Rep 2018;17:1141-7.
4Bermejo Martin JF, Jimenez JL, Muńoz-Fernández A. Pentoxifylline and severe acute respiratory syndrome (SARS): A drug to be considered. Med Sci Monit 2003;9:SR29-34.
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6Amvros'eva TV, Votiakov VI, Andreeva OT, Vladyko GV, Nikolaeva SN, Orlova SV, et al. New properties of trental as an inhibitor of viral activity with a wide range of activity. Vopr Virusol 1993;38:230-3.
7Chen YM, Wu KD, Tsai TJ, Hsieh BS. Pentoxifylline inhibits PDGF-induced proliferation of and TGF-beta-stimulated collagen synthesis by vascular smooth muscle cells. J Mol Cell Cardiol 1999;31:773-83.